1od9: Difference between revisions
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==Overview== | ==Overview== | ||
The Siglec family of receptors mediates cell surface interactions through | The Siglec family of receptors mediates cell surface interactions through recognition of sialylated glycoconjugates. The crystal structure of the N-terminal immunoglobulin-like domain of the Siglec sialoadhesin (SnD1) in complex with 2,3-sialyllactose has informed the design of sialic acid analogs (sialosides) that bind Siglecs with significantly enhanced affinities and specificities. Binding assays against sialoadhesin (Sn; Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4) show a 10- to 300-fold reduction in IC(50) values (relative to methyl-alpha-Neu5Ac) for three sialosides bearing aromatic group modifications of the glycerol side chain: Me-alpha-9-N-benzoyl-amino-9-deoxy-Neu5Ac (BENZ), Me-alpha-9-N-(naphthyl-2-carbonyl)-amino-9-deoxy-Neu5Ac (NAP), and Me-alpha-9-N-(biphenyl-4-carbonyl)-amino-9-deoxy-Neu5Ac (BIP). Crystal structures of these sialosides in complex with SnD1 suggest explanations for the differences in specificity and affinity, providing further ideas for compound design of physiological and potentially therapeutic relevance. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Brossmer, R.]] | [[Category: Brossmer, R.]] | ||
[[Category: Crocker, P | [[Category: Crocker, P R.]] | ||
[[Category: Jones, E | [[Category: Jones, E Y.]] | ||
[[Category: Kelm, S.]] | [[Category: Kelm, S.]] | ||
[[Category: Maenaka, K.]] | [[Category: Maenaka, K.]] | ||
[[Category: Maenaka, T.]] | [[Category: Maenaka, T.]] | ||
[[Category: Zaccai, N | [[Category: Zaccai, N R.]] | ||
[[Category: BND]] | [[Category: BND]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
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[[Category: siglec]] | [[Category: siglec]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:16:19 2008'' | ||
Revision as of 15:16, 21 February 2008
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N-TERMINAL OF SIALOADHESIN IN COMPLEX WITH ME-A-9-N-BENZOYL-AMINO-9-DEOXY-NEU5AC (BENZ COMPOUND)
OverviewOverview
The Siglec family of receptors mediates cell surface interactions through recognition of sialylated glycoconjugates. The crystal structure of the N-terminal immunoglobulin-like domain of the Siglec sialoadhesin (SnD1) in complex with 2,3-sialyllactose has informed the design of sialic acid analogs (sialosides) that bind Siglecs with significantly enhanced affinities and specificities. Binding assays against sialoadhesin (Sn; Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4) show a 10- to 300-fold reduction in IC(50) values (relative to methyl-alpha-Neu5Ac) for three sialosides bearing aromatic group modifications of the glycerol side chain: Me-alpha-9-N-benzoyl-amino-9-deoxy-Neu5Ac (BENZ), Me-alpha-9-N-(naphthyl-2-carbonyl)-amino-9-deoxy-Neu5Ac (NAP), and Me-alpha-9-N-(biphenyl-4-carbonyl)-amino-9-deoxy-Neu5Ac (BIP). Crystal structures of these sialosides in complex with SnD1 suggest explanations for the differences in specificity and affinity, providing further ideas for compound design of physiological and potentially therapeutic relevance.
About this StructureAbout this Structure
1OD9 is a Single protein structure of sequence from Mus musculus with and as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Structure-guided design of sialic acid-based Siglec inhibitors and crystallographic analysis in complex with sialoadhesin., Zaccai NR, Maenaka K, Maenaka T, Crocker PR, Brossmer R, Kelm S, Jones EY, Structure. 2003 May;11(5):557-67. PMID:12737821
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